Mechanism of Diels-Alder reaction

The observation that the transition state volumes in many Diels-Alder reactions are product-like, has been regarded as an indication of a concerted mechanism. In order to test this hypothesis and to gain further insight into the often more complex mechanism of Diels-Alder reactions, the effect of pressure on competing [4 + 2] and [2 + 2] or [4 + 4] cycloadditions has been investigated. In competitive reactions the difference between the activation volumes, and hence the transition state volumes, is derived directly from the pressure dependence of the product ratio, [4 + 2]/[2 + 2]p = [4 + 2]/[2 + 2]p=i exp —< AF (p — 1)/RT. All [2 + 2] or [4 + 4] cycloadditions listed in Tables 3 and 4 doubtlessly occur in two steps via diradical intermediates and can therefore be used as internal standards of activation volumes expected for stepwise processes. Thus, a relatively simple measurement of the pressure dependence of the product ratio can give important information about the mechanism of Diels-Alder reactions. 

S. Sakai, Theoretical Analysis of Concerted and Stepwise Mechanisms of Diels-Alder Reaction Between Butadiene and Ethylene. J. Phys. Chem. A, 2000, 104, 922-927. 

Since the Diels-Alder reaction is both experimentally and theoretically well characterized, we now have a thorough understanding of this important transfonnation. This allowed one to influence rates and selectivities of this cycloaddition. An illustrative example is the selective synthesis of a key prostaglandine precursor (Scheme 2) in which all stereochemical information derives from the starting materials. Although the general mechanism of Diels-Alder reactions is well understood, it is still uncertain if these reactions occur in biosynthesis. An instructive example is represented by the total synthesis of optically active plagiospirohdes 1 and 2 (Scheme 3) -. These syntheses were considered to be biomimetic and are indications that Diels-Alder reactions may also occur in vivo. 

Scheme 8.15. Possible mechanisms of Diels-Alder reactions.

Transition state structures are for s3mchronous concerted mechanism of Diels Alder reactions and are very similar to each other. The two isomeric structures for the cyclopropene addition to 1,2,5-oxadiazole are presented in Figure 9. Sometimes the AMI semiempirical method can compute as3Tnmetric transition state structures that are, in energy, very close to the symmetric transition state structures presented in Figure 9. 

What is the rmderl3ring mechanism of Diels-Alder reaction ... 

Now let us look more closely at the scope and limitations, stereochemistry, and mechanism of Diels-Alder reactions. 

Inverse Electron Demand Diels-Alder Reation Fig. 2.4 Mechanism of Diels-Alder reaction [1, 2]... 

This thesis contributes to the knowledge of catalysis in water, us it describes an explorative journey in the, at the start of the research, unh odded field of catalysis of Diels-Alder reactions in aqueous media. The discussion will touch on organic chemistry, coordination chemistry and colloid chemistry, largely depending upon the physical-organic approach of structural variation for the elucidation of the underlying mechanisms and principles of the observed phenomena. 

Luche and coworkers [34] investigated the mechanistic aspects of Diels-Alder reactions of anthracene with either 1,4-benzoquinone or maleic anhydride. The cycloaddition of anthracene with maleic anhydride in DCM is slow under US irradiation in the presence or absence of 5% tris (p-bromophenyl) aminium hexachloroantimonate (the classical Bauld monoelectronic oxidant, TBPA), whereas the Diels Alder reaction of 1,4-benzoquinone with anthracene in DCM under US irradiation at 80 °C is slow in the absence of 5 % TBPA but proceeds very quickly and with high yield at 25 °C in the presence of TBPA. This last cycloaddition is also strongly accelerated when carried out under stirring solely at 0°C with 1% FeCh. The US-promoted Diels Alder reaction in the presence of TBPA has been justified by hypothesizing a mechanism via radical-cation of diene, which is operative if the electronic affinity of dienophile is not too weak. 

Wang, H. Wang, Y. Han, K.-L. Peng, X.-J. A DFT study of Diels-Alder reactions of o-quinone methides and various substituted ethenes selectivity and reaction mechanism. J. Org. Chem. 2005, 70, 4910-4917. 

According to recent quantum mechanical calculations, die importance of secondary orbital interactions, which have also been frequently used to explain die endo diastereoselectivity of Diels-Alder reactions, seems to be questionable and to be reserved for special cases like the addition of cyclopropene to various dienes. T. Karcher, W. Sicking, J. Sauer and R. Sustmann, Tetrahedron Lett., 33, 8027 (1992) R. Sustmann and W. Sicking, Tetrahedron, 48, 10293 (1992) Y. Apeloig and E. Matzner,./. Am. Chem. Soc., 117, 5375 (1995). 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

As a consequence of the concerted mechanism, the Diels-Alder reaction is also stereoselective, implying that the relative configuration of the groups of the reactants is retained. Besides the numerous examples of heterosubstituted compounds,521,522 this was also proved by 1,3-butadiene and ethylene labeled with deuterium [Eqs. (6.88) and (6.89)] 531... 

The rates of Diels-Alder reactions are little affected by the polarity of the solvent. If a zwitterionic intermediate were involved, the intermediate would be more polar than either of the starting materials, and polar solvents would solvate it more thoroughly. Typically, a large change of solvent dipole moment, from 2.3 to 39, causes an increase in rate by a factor of only 10. In contrast, stepwise ionic cycloadditions take place with increases in rate of several orders of magnitude in polar solvents. This single piece of evidence rules out stepwise ionic pathways for most Diels-Alder reactions, and the only stepwise mechanism left is that involving a diradical. 

Mayo [16] proposed an alternative mechanism that is currently widely supported. Figure 7.7 shows a schematic of the Mayo mechanism. A Diels-Alder reaction between two styrene molecules produces an intermediate dimer (DH), also referred to as Mayo dimer . DH is highly reactive and has never been isolated. To complete the auto-initiation, DH reacts with a third styrene molecule via molecular assisted homolysis [17] to form a phenyltetraline radical (D ) and a phenethyl radical (SH ). A second reaction involving DH is to undergo chain transfer with a growing radical chain to produce a dead polymer chain (PS-H) and a new growing radical. The chain transfer constant (A ct) of DH has been estimated at 10, which is the highest Kcl ever reported for a molecule that contains no heteroatoms [18,19]. 

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